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TPS6096 Background: High-risk locally advanced cervical cancer has a poor prognosis, and more than half of patients recur in 2 y. External beam radiotherapy (EBRT) with concurrent chemotherapy followed by brachytherapy is the standard of care for locally advanced cervical cancer. The immunostimulatory activity of the PD-1 inhibitor pembrolizumab (pembro) may be enhanced by concurrent chemoradiotherapy (CRT). After the KEYNOTE-158 study, in which pembro showed durable antitumor activity, pembro monotherapy was approved for patients with PD-L1–positive recurrent or metastatic cervical cancer who progressed during or after chemotherapy. ENGOT-cx11/KEYNOTE-A18 (NCT04221945) is a phase III, randomized, placebo-controlled study evaluating pembro with concurrent CRT for the treatment of locally advanced cervical cancer. Methods: Approximately 980 patients with high-risk (FIGO 2014 stage IB2-IIB with node-positive disease or stage III-IVA), locally advanced, histologically confirmed cervical cancer who have not received systemic therapy, immunotherapy, definitive surgery, or radiation will be randomized 1:1 to receive either 5 cycles of pembro 200 mg every 3 wk (Q3W) + CRT followed by 15 cycles of pembro 400 mg Q6W or 5 cycles of placebo Q3W + CRT followed by 15 cycles of placebo Q6W. The CRT regimen includes 5 cycles (with optional 6th dose) of cisplatin 40 mg/m2 Q1W + EBRT followed by brachytherapy. Randomization is stratified by planned EBRT type (intensity-modulated radiotherapy [IMRT] or volumetric-modulated arc therapy [VMAT] vs non-IMRT or non-VMAT), cancer stage at screening (stage IB2-IIB vs III-IVA), and planned total radiotherapy dose. Treatment will continue until the patient has received 20 cycles of pembro (5 cycles 200 mg Q3W, 15 cycles 400 mg Q6W) vs placebo (~2 y) or until disease progression, unacceptable toxicity, or withdrawal. Primary endpoints are PFS per RECIST v1.1 by blinded independent central review and OS. Secondary endpoints are PFS at 2 y, OS at 3 y, complete response at 12 wk, ORR, PFS and OS in PD-L1–positive patients, EORTC QLQ-C30 and QLQ-CX24, and safety. Enrollment is ongoing. Clinical trial information: NCT04221945.

distribution of FOLR1 in normal tissues may increase it's diagnostic and therapeutic potential through targeted agents currently under development. We characterized the FOLR1 serum expression in benign and malignant ovarian pathology pre-and postoperatively. Methodology Patients with suspected ovarian cancer treated at our Institution between 2018-2021 were prospectively enrolled. Pre-and/or postoperative (1-8 days after) blood samples were taken. Quantitative measurement of FOLR1 serum concentration was carried out by ELISA. Result(s)* Median age of participating patients was 53 (range 40-78). On definitive pathology 13 (22%) patients had benign adnexal masses and 46 (78%) had serous ovarian cancer. Thirty-seven (63%) patients had FIGO stage III-IV and 15 (25%) received neoadjuvant chemotherapy (NACT). Preoperative FOLR1 was significantly higher in the malignant group versus cases with benign pathology (mean 2190 ng/mL vs 499 ng/mL, p=0.001). NACT patients had a significantly lower preoperative FOLR1 than chemotherapy naïve patients (mean 1001 ng/mL vs 2765 ng/mL, p=0.012). Additionally, the preoperative FOLR1 in chemotherapy naïve patients was significantly higher in advanced-stage disease FIGO III-IV versus early-stage disease FIGO I-II (3317 ng/mL vs 1179 ng/mL, p=0.023). In paired pre-and postoperative samples no significant FOLR1 difference was noted (n=19, p=0.64), however for paired samples taken up to 3 days postoperatively a significant increase was seen in the postoperative value (1547 ng/ mL vs 1768 ng/mL, p=0.047, n=7). Interestingly, 1/7 (14%) cases demonstrated a decrease in postoperative FOLR1 in the first 3 days while 8/12 (66.6%) cases had a decrease in postoperative FOLR1 4-8 days after (p=0.027). Conclusion* Elevated serum FOLR1 values correlated with malignancy and advanced stage while NACT significantly reduced FOLR1 values, in correlation with disease burden. We describe here a significant postoperative surge of FOLR1 that decreases >3 days after surgery that requires subsequent investigation. The full diagnostic and therapeutic potential of FOLR1 is yet to be explored and further analysis in corresponding tissue samples is ongoing.